Insulin-like growth factors that help cancer cells resist chemotherapy and radiation can be blocked by insulin-like growth factor binding protein-3 (IGFBP-3), but it is believed that the Ras gene, which plays a role in cell growth and differentiation, eventually makes IGFBP-3 less effective. Dr. Ho-Young Lee of M.D. Anderson Cancer Center and colleagues tested whether a combination of both IGFBP-3 and SCH66336, a Ras-blocking agent, increased apoptosis in non-small-cell lung cancer (NSCLC) cells. Study results are published in the October 20 Journal of the National Cancer Institute.
The research was conducted both in vitro and in vivo, in mice, with normal human bronchial epithelial cells as a control. Results showed that for both in vitro and in vivo, the combination of IGFBP-3 and SCH66336 synergistically increased apoptosis while also decreasing the proteins that block apoptosis. After 16 days in the in vivo model, mice that received the combination had tumors that were less than half the size of those that did not, suggesting that the combination of these agents has the potential for being an effective therapy for NSCLC. The authors speculate that a possible mechanism for this effect could be decreased stability of Akt, a protein that affects Ras, and note that suppression of Akt and its complement, PI3K, may be necessary when designing future IGFBP-3 therapies.
Compared with postoperative chemoradiotherapy, which is the standard treatment for patients with locally advanced rectal cancer, preoperative chemoradiotherapy improves local control of the disease and reduces toxicity, according to a study published in the October 21 New England Journal of Medicine. The study was sponsored by Deutsche Krebshilfe, a German nonprofit organization.
Between 1994 and 2002, 823 rectal cancer patients from 26 European hospitals were randomly assigned to either preoperative or postoperative chemoradiotherapy. Study endpoints, including overall survival, acute and long-term toxic effects of treatment, local and distant disease recurrence, and sphincter preservation, were measured at a median follow-up time of nearly 46 months.
At follow-up, only 25 percent of patients in the preoperative group showed metastasis to the lymph nodes, compared with 40 percent of patients in the postoperative group. Scientists also reported statistically better sphincter preservation in the preoperative group, as well as lower overall rates of acute and long-term toxic effects. There were no significant differences, however, in 5-year survival rates between the two groups.
The authors note that although no survival benefit was observed, "preoperative chemoradiotherapy is the preferred treatment for patients with locally advanced rectal cancer, given that it's associated with...an improved rate of local control, reduced toxicity, and an increased rate of sphincter preservation in patients with low-lying tumors."
Radiolabeled antibodies targeting the skin pigment molecule melanin have been shown to be effective in treating melanoma tumors in mice, according to a paper in the October 12 Proceedings of the National Academy of Sciences. In addition, the research team, from Albert Einstein College of Medicine and Cornell University, found that this approach, known as immunoradiotherapy, spared healthy tissue surrounding cancer sites, delivering radiation only to melanoma tumors.
The research team created a melanin antibody from the fungus C. neoformans and labeled it with rhenium. They found that the antibody attached to several types of cells from various mouse melanoma cell lines. When the radioactive antibody was administered to mice with melanoma, it inhibited their tumor growth and prolonged their survival. The mice that received treatment showed no kidney damage, nor did they show histological evidence of radiation damage to the skin, hair follicles, or eyes.
The authors note that although melanin exists in both cancerous and healthy cells, this strategy is effective because melanin in normal cells is relatively shielded from the radiolabeled antibodies, whereas the rapid turnover and lysis of cancerous cells releases melanin into the surrounding extracellular space, where it becomes more accessible to treatment. Furthermore, melanin has become a good candidate for therapy because of its ability to accumulate and remain in targeted tissues for longer periods of time compared with other traditional tumor antigens.